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The acidic tumor microenvironment enhances PD-L1 expression via activation of STAT3 in MDA-MB-231 breast cancer cells.
Kwon, Yong-Jin; Seo, Eun-Bi; Jeong, Ae Jin; Lee, Song-Hee; Noh, Kum Hee; Lee, Sangsik; Cho, Chung-Hyun; Lee, Chang-Han; Shin, Hyun Mu; Kim, Hang-Rae; Moon, Hyeong-Gon; Ye, Sang-Kyu.
Afiliação
  • Kwon YJ; Department of Pharmacology and Biomedical Sciences, Seoul National University College of Medicine, Seoul, 03080, Republic of Korea.
  • Seo EB; Biomedical Science Project (BK21PLUS), Seoul National University College of Medicine, Seoul, 03080, Republic of Korea.
  • Jeong AJ; Department of Pharmacology and Biomedical Sciences, Seoul National University College of Medicine, Seoul, 03080, Republic of Korea.
  • Lee SH; Biomedical Science Project (BK21PLUS), Seoul National University College of Medicine, Seoul, 03080, Republic of Korea.
  • Noh KH; Department of Pharmacology and Biomedical Sciences, Seoul National University College of Medicine, Seoul, 03080, Republic of Korea.
  • Lee S; Department of Pharmacology and Biomedical Sciences, Seoul National University College of Medicine, Seoul, 03080, Republic of Korea.
  • Cho CH; Department of Pharmacology and Biomedical Sciences, Seoul National University College of Medicine, Seoul, 03080, Republic of Korea.
  • Lee CH; Department of Biomedical Engineering, Catholic Kwangdong University College of Medical Convergence, Gangneung, 25601, Republic of Korea.
  • Shin HM; Department of Pharmacology and Biomedical Sciences, Seoul National University College of Medicine, Seoul, 03080, Republic of Korea.
  • Kim HR; Department of Pharmacology and Biomedical Sciences, Seoul National University College of Medicine, Seoul, 03080, Republic of Korea.
  • Moon HG; Wide River Institute of Immunology, Seoul National University, Hongcheon, 25159, Republic of Korea.
  • Ye SK; Department of Anatomy and Cell Biology, Seoul National University College of Medicine, Seoul, 03080, Republic of Korea.
BMC Cancer ; 22(1): 852, 2022 Aug 04.
Article em En | MEDLINE | ID: mdl-35927628
ABSTRACT
Tumor acidosis, a common phenomenon in solid cancers such as breast cancer, is caused by the abnormal metabolism of cancer cells. The low pH affects cells surrounding the cancer, and tumor acidosis has been shown to inhibit the activity of immune cells. Despite many previous studies, the immune surveillance mechanisms are not fully understood. We found that the expression of PD-L1 was significantly increased under conditions of extracellular acidosis in MDA-MB-231 cells. We also confirmed that the increased expression of PD-L1 mediated by extracellular acidosis was decreased when the pH was raised to the normal range. Gene set enrichment analysis (GSEA) of public breast cancer patient databases showed that PD-L1 expression was also highly correlated with IL-6/JAK/STAT3 signaling. Surprisingly, the expression of both phospho-tyrosine STAT3 and PD-L1 was significantly increased under conditions of extracellular acidosis, and inhibition of STAT3 did not increase the expression of PD-L1 even under acidic conditions in MDA-MB-231 cells. Based on these results, we suggest that the expression of PD-L1 is increased by tumor acidosis via activation of STAT3 in MDA-MB-231 cells.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Neoplasias da Mama / Antígeno B7-H1 Limite: Female / Humans Idioma: En Ano de publicação: 2022 Tipo de documento: Article

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Neoplasias da Mama / Antígeno B7-H1 Limite: Female / Humans Idioma: En Ano de publicação: 2022 Tipo de documento: Article